Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID)
Severe Combined Immunodeficiency
About this trial
This is an interventional treatment trial for Severe Combined Immunodeficiency focused on measuring Severe Combined Immunodeficiency, SCID, TCRα/β/CD19-depleted graft, CD45RA-depleted DLI, Graft-Versus-Host-Disease, Transplant
Eligibility Criteria
Inclusion Criteria - Transplant Recipient
- Age ≥2 months old at the time of chemotherapy administration
- A proven mutation as defined by direct sequencing of patient DNA
- Has a suitable matched sibling donor or matched unrelated donor (8/8) or single haplotype matched (≥3 of 6) family member donor
- Patient must fulfill pre-transplant evaluation:
- Left ventricular ejection fraction >40% and no evidence of uncorrected congenital malformation with clinical symptomatology
- Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2 or serum Creatinine ≤1.2mg/dL
- Resting pulse oximetry ≥90% on room or ≥95% on oxygen supplementation
- Lansky (age-dependent) performance score ≥50
- Bilirubin ≤3 times the upper limit of normal for age
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age
Exclusion Criteria - Transplant Recipient
- Positive for HIV infection by genome PCR
- Presence of active malignancy
- A social situation indicating that the family may not be able to comply with protocol procedures and recommended medical care
- Presence of a medical condition indicating that survival will be dismal such as the requirement for mechanical ventilation, severe failure of a major organ system, or evidence of a serious, progressive infection that is refractory to medical therapy
Inclusion Criteria - Matched Sibling Donor and Haplocompatible Donor
- Fully matched sibling donor (8/8), or matched unrelated donor (8/8), or at least single haplotype matched (≥3 of 6) family member
- At least 1 year old (MSD) and at least 18 years of age (Haplocompatible)
- HIV negative
- Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female)
- Not breast feeding
Regarding donation eligibility, is identified as either:
- Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR
- Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271
Sites / Locations
- St. Jude Children's Research Hospital
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
TCRα/β/CD19-depleted SCT
Donor Lymphocyte Infusions
A preparative regimen based on the type of SCID will be given followed by infusion of donor cells. Cells for infusion are prepared using the CliniMACS System Regimen 1 - IL2RG, JAK 3 (Haplocompatible) and all MSD ATG (rabbit) IV Days -9 -8 and -7, Rest Days -6 and -5, Busulfan IV Days -4, -3, and -2, Rest Day -1, TCRα/β/CD19-depleted SCT, Day 0 Regimen 2 - RAG1, RAG2 (Haplocompatible) ATG (rabbit) IV Days -9 -8 and -7, Fludarabine IV Days -7, -6, -5 and -4, Busulfan IV Days -5, -4 and -3, Thiotepa IV twice daily, Day -2, Rest Day -1, TCRα/β/CD19-depleted SCT, Day 0 Regimen 3 - ADA, IL7R, CD45 deficiency, CD3 subunits (Haplocompatible) ATG (rabbit) IV Days -9 -8 and -7, Fludarabine IV Days -7, -6, -5 and -4, Busulfan: IV Days -4, -3 and -2, Rest Day -1, TCRα/β/CD19-depleted SCT, Day 0
Phase I: On the Phase I portion of the study, up to 4 different dose levels will be evaluated: Dose level -1, Dose ≥0.1 to ≤0.3; Dose level 1, Dose >0.3 to ≤0.56; Dose level 2, Dose >0.56 to ≤1.8; Dose level 3, Dose >1.80 to ≤3.0 Dosing is determined based on the number of CD3+CD45RA-cells/kg and the patient weight in kilograms. Phase II: Participants will receive the Phase I determined maximum tolerated dose (MTD) of DLI. Cells for infusion are prepared using the CliniMACS System.